Pharmacology of Drugs for Neurodegenerative Disorders

Question 1

What anticholinergic drugs are used to treat Parkinson’s?

Answer 1

Benztropine, trihexyphenidyl

Question 2

What life-threatening ADRs are associated with use of MOA inhibitors?

Answer 2

Hypertensive crisis and serotonin syndrome in patients on TCAs or SSRIs

Question 3

What is the primary strategy for the use of drugs to treat Parkinson’s disease?

Answer 3

In Parkinson’s disease, less dopamine is present in the synaptic cleft. The target of drugs is to increase or amplify functional dopamine

Question 4

What is the MOA of Selegiline?

Answer 4

A selective, irreversible inhibitor of MOA-B. This drug cannot be used as a monotherapy

Question 5

Amantadine should be used cautiously in what patient populations?

Answer 5

Patients with seizures, heart failure, or renal failure

Question 6

This drug is a dopamine precursor the works to increase the presence of dopamine at the synaptic cleft.

Answer 6

Levodopa

Question 7

What is the MOA of Riluzole?

Answer 7

Antioxidant that reduces glutamate-induced excitotoxicity of ALS

Question 8

What antipsychotic does not target D2 receptors and may be used to treat psychosis in a patient with Parkinson’s disease?

Answer 8

Primavanserin

Question 9

Hallucinations are associated with what MOA inhibitor?

Answer 9

Selegiline

Question 10

What are the COMT inhibitors used to treat Parkinson’s?

Answer 10

Entacapone & Tolcapone

Question 11

What is the MOA of Lecanemab?

Answer 11

Monoclonal antibody against amyloid beta plaques

Question 12

What is the MOA of anticholinergic medications in treating Parkinson’s?

Answer 12

Dampen stimulatory signaling from neurons

Question 13

What is the most common dopamine agonist used to treat Parkinson’s disease?

Answer 13

Pramipexole

Question 14

Impulse control disorders are associated with what MOA inhibitor?

Answer 14

Rasagiline

Question 15

What is the only drug used to treat Alzheimer’s that reduces the rate of disease progression and slows cognitive decline?

Answer 15

Lecanemab

Question 16

Levodopa is quickly converted to dopamine in circulation and cannot cross the BBB. How can this issue be resolved?

Answer 16

Co-treatment with a DOPA decarboxylase inhibitor. L-DOPA can cross the BBB, where there it can be converted to dopamine by a DOPA decarboxylase

Question 17

Symptoms of parkinsonism induced by drugs typically resolve within 6 months of drug withdrawal. What drug is the exception?

Answer 17

Synthetic heroin (MPTP) - symptoms are irreversible and progressive degeneration of neurons may occur for years

Question 18

What drug is used as a rescue therapy for temporary relief of off-periods of akinesia?

Answer 18

Apomorphine

Question 19

These categories of Parkinson’s drugs work to prevent the breakdown of dopamine.

Answer 19

DOPA decarboxylase inhibitors, Catechol-O-methyltransferase inhibitors (COMTIs), Monoamine oxidase B inhibitors (MOA inhibitors)

Question 20

What is the MOA of tetrabenazine?

Answer 20

Depletes cerebral dopamine to reduce severity of chorea

Question 21

True/False. Levodopa may be used as a chronic monotherapy to treat motor symptoms of Parkinson’s disease.

Answer 21

False. The benefits of Levodopa begin to decline after 3-5 years. Other drugs may be added to enhance the effects of Levodopa, but decreased efficacy and response fluctuations will occur

Question 22

What serious ADR is associated with monoclonal antibody treatment of Alzheimer’s?

Answer 22

Intracerebral hemorrhages

Question 23

True/False. A patient failed treatment with L-dopa. Treatment with Pramipexole is an effective next treatment option.

Answer 23

False. Dopamine agonists are generally ineffective in patients who did not respond to L-dopa.

Question 24

What NMDA Antagonist is used to improve cognition in patients with early Alzheimer’s?

Answer 24

Memantine

Question 25

Anticholinergics should not be used to treat Parkinson's in what patients?

Answer 25

Elderly and cognitively impaired, patients with bradykinesia

Question 26

What are the contraindications for the use of L-dopa?

Answer 26

Closed-angle glaucoma, psychosis, melanoma or undiagnosed skin lesions, cardiac disease, gastric ulcer

Question 27

What DOPA decarboxylase inhibitor is typically administered with Levodopa?

Answer 27

Carbidopa (Benserazide is another inhibitor)

Question 28

What are the stages of treatment with Levodopa?

Answer 28

Honeymoon phase (dramatic improvement), benign fluctuations in response (wearing-off reactions, end-of-dose akinesia), unpredictable response fuctuations

Question 29

What is the MOA of Amantadine?

Answer 29

NMDA receptor antagonist that potentiates dopaminergic effects

Question 30

What is the MOA of donepezil, rivastigmine, and galantamine in treating Alzheimer's?

Answer 30

Cholinesterase inhibitors that enhance cholinergic functioning in the basal forebrain for cognition and functioning

Question 31

What MOA inhibitor is a selective, irreversible inhibitor of MOA-B, but may be administered as a monotherapy in early Parkinson's treatment.

Answer 31

Rasagiline. Selegiline is also an irreversible, selective MOA-B inhibitor, but is always used as an adjunct therapy

Question 32

What drugs are known to interact with L-dopa?

Answer 32

Vitamin B6, antiemetics, antipsychotics, MAO-A inhibitors

Question 33

What ADRs are associated with L-dopa?

Answer 33

Dyskinesias (especially twitching of face and extremities), GI disturbances, cardiac arrhythmias, orthostatic hypotension, depression, anxiety, confusion, and psychosis

Question 34

What is the only Parkinson's medication that can be used as short-term treatment for bradykinesia, rigidity, and tremor?

Answer 34

Amantadine

Question 35

What drug is used to treat ALS?

Answer 35

Riluzole

Question 36

What drugs are known to induce Parkinsonism?

Answer 36

Antipsychotics, antiemetics, synthetic heroin (MPTP)

Question 37

What ADRs are associated with COMT inhibitors?

Answer 37

Dyskinesias, GI disturbances, confusion, orthostatic hypertension, urine discoloration

Question 38

What COMT inhibitor is most commonly used, even though it is less effective?

Answer 38

Entacapone - Tolcapone is more effective but has high risk of hepatotoxicity

Question 39

What drug is used to reduce movement in patients with Huntington's Disease?

Answer 39

Tetrabenazine

Question 40

What is the oral form of Riluzole for ALS treatment?

Answer 40

Edaravone

Question 41

ADRs of dopamine agonists are similar to those of L-dopa. What additional ADRs are present?

Answer 41

Dopamine agonists withdrawal syndrome, dopaminergic dysregulation syndrome, sleep attacks

Question 42

True/False. L-dopa, dopa decarboxylase inhibitors, and COMT inhibitors may all be administered to treat Parkinson's and work to increase dopamine presence.

Answer 42

True. The combined drug is called Stalevo. This is commonly useful when patients reach the phase of response fluctuations with L-dopa alone

Question 43

What ADRs are most commonly associated with cholinesterase inhibitors in treating Alzheimer's?

Answer 43

GI disturbances, bradycardia, hypotension, sleep distubrances

Question 44

Dopamine agonists are contraindicated in what patients?

Answer 44

Patients with history of psychosis, myocardial infarction, peptic ulcers

Question 45

Parkinson's disease is characterized by demyelination of neurons in the substantia nigra. Where do these neurons project?

Answer 45

Striatum (Caudate & Putamen)

Question 46

Riluzole and Edaravone have limited effects on the disease progression of ALS. What drugs are used solely for symptomatic treat of ALS?

Answer 46

Baclofen (spasticity) & Gabapentin (slow muscle atrophy)

Question 47

Peripheral edema and livedo reticularis are ADRs associated with what Parkinson's medication?

Answer 47

Amantadine